The cell is the smallest unit of life. Through many decades of research, scientists have come to view the living cell as a kind of ''factory'' wherein specialized machinery carries out essential tasks at specific times and places. The cell's molecular machines behave as minuscule, nanometer-size engines. They perform tasks as diverse as maintaining the genome's integrity, transporting cargo around the cell, and moving the cells themselves. The last twenty years has seen the emergence of a new field called ''single-molecule biophysics'' that has revolutionized our understanding of these machines. Using tools from the physical sciences, researchers are now able to study biomolecular machines one at a time in unprecedented detail. In this talk, I will discuss the state of the art in this field, what new insights have emerged and how these studies relate to human health and disease.